Novel polymorphisms of the amyloid precursor protein (APP) gene in Chinese/Taiwanese patients with Alzheimer's disease.

We aimed to determine if the amyloid precursor protein (APP) gene polymorphism is present in Chinese/Taiwanese patients with Alzheimer's disease (AD). This is a 3-year prospective assessment of the genotypes of the APP gene among Chinese/Taiwanese patients with AD. The sample consisted of 50 AD patients and 50 unaffected controls. Participants were recruited from the practices of the authors. Controls were comprised of 45 unrelated healthy subjects and 5 unaffected family members of AD patients. Data were collected in a university-based research unit of a tertiary medical center. Sequencing of the APP gene from exon 15 to exon 18 was performed on the peripheral blood of the patients and the unaffected controls after their informed consent was obtained. Among 50 AD subjects, 11 (7 men, 4 women) had APP gene polymorphisms. Mean age of onset was 72 years (range 65-82 years). Polymorphism of APP gene with A to C substitution at nucleotide position (nt) 284490 (A284490C) was found in 8 AD patients, at nt 284493 (A284493C) in 5, T284497C in 3 patients, and T284500C in 1 patient. These single nucleotide substitutions of the APP gene corresponded to the amino acid substitutions I718L, L720S, and V710G. These polymorphisms were not found in the unaffected controls. The mutations were confirmed by StyI restriction enzyme digestion assay using the subclone from polymerase chain reaction (PCR) products of the mutated APP gene. Thus, APP gene polymorphisms at codon 718 (I>L), 720 (L>S), and 710 (V>G) can be found in certain Chinese/Taiwanese patients with Alzheimer's disease.